Out of (West) Africa-Who Lost in the End?

On October 29, 2014, 4 days before the annual meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) to be held in New Orleans, LA, meeting registrants received an e-mail letter from the Louisiana Department of Health and Hospitals stating "we have requested that any individuals that will be traveling to Louisiana following a trip to the West African countries of Guinea, Liberia, and Sierra Leone or have had contact with an Ebola-infected individual remain in a self-quarantine for the 21 days following their relevant travel history…we see no use in you traveling to New Orleans to simply be confined to your room." This communication made it clear that those recently in countries experiencing the 2014 Ebola epidemic would not be able to participate in the meeting. The ASTMH sent their own communication stating that the Society did not agree with the State's policy, but had no choice but to abide. However inconvenient and upsetting this decision might have been, what really matters transcends the mere disturbance of long-planned schedules. More broadly, we lost on five levels

A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study

BACKGROUND:Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded.Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. Overall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. However, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies (ACTs) and especially artemether-lumefantrine in malnourished children is currently lacking.The main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition (SAM) compared to non-SAM children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile.METHODS/DESIGN:In two sites, Ouelessebougou, Mali and Maradi, Niger, children with uncomplicated microscopically-confirmed P. falciparum malaria aged between 6 and 59 months will be enrolled. Two non-SAM children will be enrolled after the enrolment of each SAM case. Children with severe manifestations of malaria or complications of acute malnutrition needing intensive treatment will be excluded.Treatment intakes will be supervised and children will be followed-up for 42 days, according to WHO guidance for surveillance of antimalarial drug efficacy. Polymerase Chain Reaction genotyping will be used to distinguish recrudescence from re-infection. SAM children will also benefit from the national nutritional rehabilitation program.Outcomes will be compared between the SAM and non-SAM populations. The primary outcome will be adequate clinical and parasitological response at day 28 after PCR correction, estimated by Kaplan-Meier analysis. To assess the pharmacokinetic profile of lumefantrine, a sparse sampling approach will be used with randomized allocation of sampling times (5 per child). A total of 180 SAM children and 360 non-SAM children will be recruited during the 2013 and 2014 malaria seasons.DISCUSSION:This study will provide important information that is currently lacking on the effect of SAM on therapeutic efficacy and pharmacokinetic profile of artemether-lumefantrine. If it shows lower therapeutic efficacy and decreased lumefantrine concentrations, it would inform dose optimization studies in SAM children.TRIAL REGISTRATION:ClinicalTrials.gov: NCT0195890

Neuropathic Pain and Psychological Morbidity in Patients with Treated Leprosy: A Cross-Sectional Prevalence Study in Mumbai

Peer reviewe

AmBisome Monotherapy and Combination AmBisome-Miltefosine Therapy for the Treatment of Visceral Leishmaniasis in Patients Coinfected With Human Immunodeficiency Virus in India: A Randomized Open-Label, Parallel-Arm, Phase 3 Trial.

BACKGROUND: Visceral leishmaniasis (VL) in patients with human immunodeficiency virus (HIV) presents an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian subcontinent. METHODS: This is a randomized, open-label, parallel-arm, phase 3 trial conducted within a single hospital in Patna, India. One hundred and fifty patients aged ≥18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to 1 of 2 treatment arms, either a total 40 mg/kg intravenous liposomal amphotericin B (AmBisome; Gilead Pharmaceuticals) administered in 8 equal doses over 24 days or a total 30 mg/kg intravenous AmBisome administered in 6 equal doses given concomitantly with a total 1.4 g oral miltefosine administered through 2 daily doses of 50 mg over 14 days. The primary outcome was intention-to-treat relapse-free survival at day 210, defined as absence of signs and symptoms of VL or, if symptomatic, negative parasitological investigations. RESULTS: Among 243 patients assessed for eligibility, 150 were recruited between 2 January 2017 and 5 April 2018, with no loss to follow-up. Relapse-free survival at day 210 was 85% (64/75; 95% CI, 77-100%) in the monotherapy arm, and 96%, (72/75; 90-100%) in the combination arm. Nineteen percent (28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse-free survival at day 210 was 90% (55/61; 82-100%) in the monotherapy and 97% (59/61; 91-100%) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm. CONCLUSIONS: Combination therapy appears to be safe, well tolerated, and effective, and halves treatment duration of current recommendations. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry India (CTRI/2015/05/005807; the protocol is available online at https://osf.io/avz7r)

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Taha Toros Arşivi, Dosya No: 220-Kaptanzade Ali Rıza Be

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

BACKGROUND: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. RESULTS: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. CONCLUSIONS: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination

Needs and Challenges in Modelling Malaria for Emergency Contexts

While modelling is an essential component for an understanding of the epidemiology of malaria, and for designing better control measures, it rarely considers the particular contexts encountered in emergency settings. By linking these situations with the transmission parameters our aim is to correct this bias and call for a better collaboration between relief actors

Impact and Lessons Learned from Mass Drug Administrations of Malaria Chemoprevention during the Ebola Outbreak in Monrovia, Liberia, 2014

Background: In October 2014, during the Ebola outbreak in Liberia healthcare services were limited while malaria transmission continued. Médecins Sans Frontières (MSF) implemented a mass drug administration (MDA) of malaria chemoprevention (CP) in Monrovia to reduce malaria-associated morbidity. In order to inform future interventions, we described the scale of the MDA, evaluated its acceptance and estimated the effectiveness. Methods: MSF carried out two rounds of MDA with artesunate/amodiaquine (ASAQ) targeting four neighbourhoods of Monrovia (October to December 2014). We systematically selected households in the distribution area and administered standardized questionnaires. We calculated incidence ratios (IR) of side effects using poisson regression and compared self-reported fever risk differences (RD) pre- and post-MDA using a z-test. Findings: In total, 1,259,699 courses of ASAQ-CP were distributed. All households surveyed (n = 222; 1233 household members) attended the MDA in round 1 (r1) and 96% in round 2 (r2) (212/222 households; 1,154 household members). 52% (643/1233) initiated ASAQ-CP in r1 and 22% (256/1154) in r2. Of those not initiating ASAQ-CP, 29% (172/590) saved it for later in r1, 47% (423/898) in r2. Experiencing side effects in r1 was not associated with ASAQ-CP initiation in r2 (IR 1.0, 95%CI 0.49–2.1). The incidence of self-reported fever decreased from 4.2% (52/1229) in the month prior to r1 to 1.5% (18/1229) after r1 (

Qualitative study of antibiotic prescription patterns and associated drivers in Sudan, Guinea-Bissau, Central African Republic and Democratic Republic of Congo

Objectives The objective of this study was to address the knowledge gap regarding antibiotic use in Medecins Sans Frontiéres (MSF) projects located in Africa by exploring antibiotic prescription and consumption habits and their drivers at different healthcare levels.Design This study used an exploratory study design through thematic analysis of semistructured, in-depth interviews, focus group discussions (FGDs) and field observations in order to understand the main drivers influencing current antibiotics prescription habits and consumption habits of patients in different geographical settings.Setting The study took place in MSF centres and towns across four countries: Guinea-Bissau, Central African Republic (CAR), Democratic Republic of Congo (DRC) and Sudan.Participants 384 respondents participated in the study, which includes project staff, prescribers, community members, patients, among other groups.Results Treatment protocols were physically present in all countries except DRC, but compliance to protocols varied across contexts. A failing health system and barriers to accessing healthcare were perceived as major drivers of overuse and inconsistent prescription practices. Patient demands influenced prescription decisions, and self-medication was commonly reported in the context of failing health systems. Additionally, there was a strong demand for quick cures and communities preferred injections over pills. Patients tended to stop antibiotic treatment once symptoms abated and had major gaps in understanding antibiotic intake instructions and functions.Conclusions While there were specific findings in each context, the larger trend from these four MSF projects in Africa indicates widespread use of antibiotics based on unclear assumptions, which are often influenced by patient demands. There needs to be a broader focus on the balance between access and excess, especially in such fragile contexts where access to healthcare is a real challenge